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Introduction: Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) has garnered substantial interest among researchers and ophthalmologists due to its high promise as a potential treatment for infectious keratitis. The aim of this study is to evaluate the efficacy and safety of high fluence PACK-CXL, using 10.0 J/cm2 (30 mW/cm2, 5 min, and 33 s) at the slit lamp.Methods: This prospective interventional, nonrandomized cohort study included 20 eyes of 20 patients with bacterial, fungal, or mixed origin keratitis who underwent high fluence PACK-CXL treatment as an adjunct therapy to conventional antimicrobial therapy per American Academy of Ophthalmology treatment guidelines. The re-epithelization time was recorded, and corneal endothelial cell density was counted before and after treatment.Results: The average re-epithelization time was 8.2 ± 2.8 days (range 3–14 days). After PACK-CXL treatment, eight patients (40%) were directly discharged, while the remained patients stayed in the hospital for an average of 5.6 ± 3.5 days. No eyes required keratoplasty. Endothelial cell density counts before and after the PACK-CXL procedure were 2,562.1 ± 397.3, and 2,564.8 ± 404.5 cells/mm2, respectively (p = 0.96).Conclusion: although it was not a randomized control trial, we conclude that high fluence PACK-CXL as an adjuvant therapy is safe with no complications observed, and efficient as time to re-epithelization was less than 14 days for all patients and no patients underwent tectonic keratoplasties. Further research is needed to compare it to the current standard of care.

Abstract Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate’s concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.

Purpose: To assess clinical outcomes of corneal cross-linking (CXL) intervention in a population diagnosed with progressive keratoconus. Methods: This single-center retrospective cohort study included consecutive patients who underwent standard CXL or accelerated CXL for progressive keratoconus at a major teaching hospital in southern Israel between January 2015 and December 2019. Patients’ medical files were reviewed, and pre-operative and post-operative data regarding demographics and clinical and tomographic characteristics were extracted and analyzed. Results: This study included 166 patients (representing 198 eyes), out of which 98 patients (123 eyes) were ethnically Bedouin, and 68 patients (75 eyes) were ethnically Jewish. Overall, 126 patients (144 eyes) had a follow-up of at least 12 months (16.84 ± 5.76). The mean patient age was 20.62 ± 7.1 years old. There were significant baseline differences between the two ethnic groups in best-corrected visual acuity (BCVA; p < 0.001), uncorrected visual acuity (UCVA; p < 0.001), mean keratometry (p = 0.028), and corneal thickness (p < 0.001). Significant changes in BCVA, UCVA, and pachymetry parameters within each group were found after 12 months. Negative binomial regression analysis showed a maximal keratometry below 55D (RR = 1.247, p < 0.001), and a standard CXL procedure (RR = 1.147, p = 0.041) are significantly related to the stability of KC after 12 months. However, the effect size of the origin of patients is negligible (RR = 1.047, p = 0.47). Conclusions: In this study, the Bedouin population suffered from more progressive keratoconus when compared to the Jewish population. CXL was significantly effective in improving BCVA and UCVA in both groups after 12 months of follow-up. The effect size of the origin of patients on the stability of KC was found to be negligible.

Abstract Traumatic brain injury (TBI) affects millions of people worldwide, many of whom are affected with post-TBI mood disorders or behavioral changes, including aggression or social withdrawal. Diminished functionality can persist for decades after TBI and delay rehabilitation and resumption of employment. It has been established that there is a relationship between these mental disorders and brain injury. However, the etiology and causal relationships behind these conditions are poorly understood. Rodent models provide a helpful tool for researching mood disorders and social impairment due to their natural tendencies to form social hierarchies. Here, we present a rat model of mental complications after TBI using a suite of behavioral tests to examine the causal relationships between changes in social behavior, including aggressive, hierarchical, depressive, and anxious behavior. For this purpose, we used multivariate analysis to identify causal relationships between the above post-TBI psychiatric sequelae. We performed statistical analysis using principal component analysis, discriminant analysis, and correlation analysis, and built a model to predict dominant-submissive behavior based on the behavioral tests. This model displayed a predictive accuracy of 93.3% for determining dominant-submissive behavior in experimental groups. Machine learning algorithms determined that in rats, aggression is not a principal prognostic factor for dominant-submissive behavior. Alternatively, dominant-submissive behavior is determined solely by the rats’ depressive-anxious state and exploratory activity. We expect the causal approach used in this study will guide future studies into mood conditions and behavioral changes following TBI.

Abstract Background Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment. Methods This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection. Results Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups. Conclusions PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871

A healthy blood–brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.

Background: Limbal stem cell deficiency (LCSD) presents several challenges. Currently, there is no clearly defined systematic approach to LSCD diagnosis that may guide surgical tactics. Methods: The medical records of 34 patients with LSCD were analyzed. Diagnostic modalities included standard (visometry, tonometry, visual field testing, slit-lamp biomicroscopy with corneal fluorescein staining, Schirmer test 1, ultrasonography) and advanced ophthalmic examination methods such as anterior segment optical coherence tomography, in vivo confocal microscopy, impression cytology, and enzyme-linked immunoassay. Results: Standard ophthalmological examination was sufficient to establish the diagnosis of LSCD in 20 (58.8%) cases, whereas advanced evaluation was needed in 14 (41.2%) cases. Depending on the results, patients with unilateral LSCD were scheduled to undergo glueless simple limbal epithelial transplantation (G-SLET) or simultaneous G-SLET and lamellar keratoplasty. Patients with bilateral LSCD with normal or increased corneal thickness were enrolled in the paralimbal oral mucosa epithelium transplantation (pLOMET) clinical trial. Conclusions: Based on the diagnostic and surgical data analyzed, the key points in LSCD diagnosis were identified, helping to guide the surgeon in selecting the appropriate surgical procedure. Finally, we proposed a novel step-by-step diagnostic algorithm and original surgical guidelines for the treatment of patients with LSCD.

Purpose: Surgical treatment of unilateral limbal stem cell deficiency (LSCD) is based on limbal stem cell transplantation. Glueless simple limbal epithelial transplantation (G-SLET) technique implements several limbal micrografts harvested from the healthy eye of the same patient into the peripheral corneal tunnels without the use of fibrin glue and human amniotic membrane., Methods: A novel customized algorithm and software for a low-energy femtosecond laser (FSL) were developed and tested using 5 pairs of isolated porcine eyes. FSL-assisted G-SLET modification was assessed in 3 clinical cases of unilateral LSCD caused by chemical burns. Corneal epithelization efficacy, best-corrected visual acuity, corneal epithelial mapping, central corneal thickness, and impression cytology with immunohistochemical examination were evaluated. All patients were followed up for 12 months postoperatively., Results: The FSL set for 100% energy and the pattern of 8 nonpenetrating vertical cuts with oblique tunnel portions having variable incision depths and diameter of 8.5 mm and higher were selected for further clinical evaluation. Clinically, stable corneal epithelialization was achieved 2 to 3 weeks after intervention. At the 6-month follow-up, all patients had a healthy corneal epithelium with limbal micrografts visible inside the corneal tunnels. Best-corrected visual acuity markedly improved in 2 cases, but not in the third case with severe corneal stromal scarring. In addition, all patients noted a full-scale reduction in subjective complaints and substantial improvement in their quality of life., Conclusions: The FSL-assisted G-SLET is a new technique for autologous limbal stem cell transplantation in patients with unilateral LSCD. It allows the standardization of corneal tunnel localization and dimensions, thereby increasing the safety of the surgical procedure., Competing Interests: M. Fabian and B. Werner are employees of the Ziemer Ophthalmic Systems manufacturer of the femtosecond laser used in this study. The authors declare that they have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)